Our overall goal in this proposal is to obtain evidence for reduced intracellular free magnesium [Mg2+] and disturbances in energy metabolism in brain and body tissues of migraine subjects both between and during an attack. We hypothesize that migraine subjects have disordered brain energy metabolism due to impaired mitochondrial oxidative phosphorylation secondary to [Mg2+] reduction. Blood and muscle studies will establish if this [Mg2+] reduction and mitochondrial disorder is generalized to other tissues. We further hypothesize that between attacks these metabolic shifts cause instability in neuronal function, which enhances the susceptibility of brain cortex to develop migraine. Studies will be carried out using 31/P magnetic resonance spectroscopy (31/P MRS). Brain regional energy metabolism pH and [Mg2+] levels will be measured during a migraine attack, during recovery and the interictal period. We expect to show that brain [Mg2+] levels will be low in migraine patients during an attack compared to normal control and tension type headache (TTH) subjects and that there is reduced brain energy metabolism, either as a result of the low [Mg2+] or due to the attack. We propose that decreased brain [Mg2+] is present between attacks and is associated with its onset. Mononuclear blood cell levels of Mg2+ will be measured by colorimetry and muscle Mg2+ by 31/PMRS to assess if systemic Mg2+ deficiency is associated with reduced Mg2+ and disordered brain energy metabolism. Utilization and recovery of high energy phosphates in skeletal muscle at rest, during repetitive muscle contraction and during recovery will be used as a measure of mitochondrial oxidative phosphorylation.